Introduction: Lymphoid leukemia, having acute(ALL) and chronic(CLL) forms, is a malignancy of the blood and bone marrow that disrupts normal lymphocyte production. It remains a major global public health concern, with a significant prevalence in the United States. This study compares mortality trends of acute and chronic Lymphoid leukemia in the U.S. population from 1999 to 2023.

Methodology: Data were extracted from the CDC WONDER database for the years 1999 to 2023, including individuals aged ≥45 years. Firstly we evaluated mortality trends among people with acute lymphoid leukemia (C91.0) and chronic lymphoid leukemia (C91.1) individually. Then, we performed a head-to-head comparison of both groups. We analyzed age-adjusted mortality rates (AAMRs) per 100,000 population as stratified by sex, race, Hispanic origin, U.S. Census regions, and 2013 urbanization categories. Joinpoint regression(JPR) was used to estimate Annual Percent Changes (APCs) and corresponding 95% confidence intervals (CIs), with statistical significance determined via Monte Carlo permutation test (p < 0.05).

Results: Between 1999-2023, a total of 20,855 deaths were attributed to acute lymphoid leukemia(AAMR: 0.72) and while 109,807 deaths were recorded due to chronic lymphoid leukemia (AAMR: 3.74). In both ALL and CLL males showed higher mortality rates than females with 51.2% and 59.6% of total deaths respectively. In ALL, males(2018-2021) and non-Hispanics(1999-2023) showed a steady trend in mortality with APC of -7.59 (95% CI: -10.2 - 1.51; p=0.077) and -0.64 (95% CI: -0.98 - -0.25; p<0.05), respectively. While in CLL, males(1999-2012) and non-Hispanics(1999-2013) displayed notable decline in mortality with APC of -1.33(95% CI: -1.58 - -1.01; p=0.00) and -36(95% CI: -1.58 - -1.05; p=0.00), respectively. Whites affected from CLL exhibited a significant downward trend in mortality from 1999-2013 with APC of -1.35(95% CI: -1.57 - -1.04; p=0.00). For ALL, the West region reported the highest AAMR 0.77 whereas for CLL, the highest AAMR(4.25) was observed in the Midwest. Among states, Oklahoma displayed the highest AAMR of 0.9 in ALL-group while Minnesota recorded the highest AAMR for CLL, at 5.07.

Conclusion: CLL related mortality exhibited a significant decline, while ALL mortality decreased only slightly. These contrasting trends indicate differences in therapeutic progress and highlight the need for continued efforts to reduce ALL-related deaths.

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